An in vitro model of human pancreas carcinogenesis was developed in which carcinoma was induced by chemical carcinogens. Dimethylnitrosamine (DMN) and methylnitrosourea (MNU) were successfully used in this model to induce pancreatic carcinoma ranging from undifferentiated carcinoma to well-differentiated papillary carcinoma. Monoclonal antibodies to parenchymal cells were used to study the modulation of surface markers during carcinogenesis. A preneoplastic step, namely ductal metaplasia, was identified in this model before the development of hyperplasia, atypia and carcinoma. It is proposed to develop antibodies specific for progenitor cells of cancer. It is further proposed to examine the effects of NNK, a tobacco-specific carcinogen on human pancreas explants. In addition to morphological studies (light microscopy), it is proposed to quantitate and relate the rate of removal of 06-methylguanine from cells in pancreas organ culture with DMN- and NNK-induced carcinoma. The availability of normal and DMN- and NNK-treated pancreas explants at various stages of carcinoma induction facilitates the development of antibodies against cell markers specific for each of the steps in carcinogenesis.